There is now considerable evidence in the literature that both endothelial and epithelial cells have elaborate intercellular junctions localized in their plasma membranes which serve as permeability barriers to the passage of ions, small solutes, and larger molecules between cells. The long range objectives of this research proposal is to study the structural and physiological properties of these tight, or occluding, junctions in order to elucidate the mechanisms utilized by cells to control transcellular permeability. As a result of these studies, further knowledge and insight will be obtained into the process of organizational biosynthesis and assembly of tight junctional complexes. The research proposed here will give us better insight into tight junctional structure, mechanisms of assembly and degradation, and eventually lead to an elucidation of the physiological processes that regulate transcellular permeability in both normal and diseased endothelium and epithelium.